Change in physician perspective on cholesterol and heart disease. Results from two national surveys.

The National Heart, Lung, and Blood Institute sponsored national telephone surveys of practicing physicians in 1983 (N = 1610) and 1986 (N = 1277) to assess attitudes and practices regarding elevated serum cholesterol levels. The 1983 survey was conducted just before the release of the results of the Lipid Research Clinics Coronary Primary Prevention Trial, which showed that a reduction in the blood cholesterol level reduced coronary heart disease. In 1986, 64% of physicians thought that reducing high blood cholesterol levels would have a large effect on heart disease, up considerably from 39% in 1983. Whereas in 1983, physicians attributed considerably less preventive value to reducing the cholesterol level than to reducing blood pressure or smoking, this disparity was substantially smaller in 1986. The median range of blood cholesterol at which diet therapy was initiated was 6.21 to 6.70 mmol/L (240 to 259 mg/dL) in 1986, down from 6.72 to 7.21 mmol/L (260 to 279 mg/dL) in 1983; the median for drug therapy was 7.76 to 8.25 mmol/L. (300 to 319 mg/dL) in 1986 and 8.79 to 9.28 mmol/L (340 to 359 mg/dL) in 1983. In 1986, 87% of physicians surveyed felt that medical evidence warranted the recommended treatment levels set forth in the 1984 National Institutes of Health Consensus Conference on Lowering Blood Cholesterol. These changes indicate that by 1986, physicians were more convinced of the benefit of lowering high blood cholesterol levels and were treating patients accordingly. The data also suggest areas for continued educational initiatives.

Change in public perspective on cholesterol and heart disease. Results from two national surveys.

The National Heart, Lung and Blood Institute, Bethesda, Md, and the Food and Drug Administration, Washington, DC, sponsored two national probability telephone surveys (N = 4000) of adults to assess attitudes and knowledge about heart disease risk from high blood cholesterol levels and the public's efforts to lower blood cholesterol levels. The first survey was conducted in 1983, before release of the results from the Lipid Research Clinics Coronary Primary Prevention Trial, which showed that a reduction in the blood cholesterol level reduced coronary heart disease; the second survey was conducted in 1986. The percentage of adults who believed that reducing high blood cholesterol levels would have a large effect on heart disease increased from 64% in 1983 to 72% in 1986, so that the importance attached to reducing high blood cholesterol levels approached that attributed to reducing smoking and high blood pressure. In 1983, 35% of adults reported that they had their cholesterol level checked vs 46% in 1986. In both years, diet changes were most frequently chosen (greater than 60%) as ways to control the blood cholesterol level; reducing dietary fat was believed to be as important as reducing dietary cholesterol. By 1986, 23% of adults reported that they made dietary changes specifically to lower their blood cholesterol level, up from 14% in 1983. These comparative data show gains in public awareness and action relating to high blood cholesterol level risk. The data can be used to develop education programs.

Structural proteins of simian virus 40.

Sodium dodecyl sulfate acrylamide gel electrophoresis of the solubilized proteins from purified simian virus 40 (SV40) virions revealed two major and two minor structural polypeptide components. The major components which comprise over 75% of the total virion were shown to be the capsid proteins by immunological and isoelectric focusing fractionation analysis. These two polypeptides have estimated molecular weights of 45,000 daltons as determined by gel electrophoresis. One of the two minor components was identified as the nucleocapsid protein and has an approximate molecular weight of 16,000. The other unidentified minor component has an average molecular weight of 29,000.

Studies on the mode of action of diphtheria toxin. IV. Specificity of the cofactor (NAD) requirement for toxin action in cell-free systems.

The ability of a number of nucleotides related to NAD to replace NAD as cofactors for inhibition by diphtheria toxin of peptide bond formation has been examined. Neither NADH nor NADP are active. Of some 14 analogues closely related structurally to NAD that have been tested, only 3-thiocarboxamide pyridine-AD is as active as NAD itself. Replacement of the 3-carboxamide group on the pyridine ring by an acetyl group, or deamination of the purine ring, resulted in derivatives with reduced activity. The results were interpreted as suggesting that NAD and certain related nucleotides are capable of specific interaction with diphtheria toxin. Using the method of equilibrium dialysis, reversible binding of 1 mole of NAD per mole of toxin has been demonstrated. Toxoid does not interact with NAD.

Studies on the mode of action of diphtheria toxin. 3. Site of toxin action in cell-free extracts.

Extracts from HeLa cells treated with excess diphtheria toxin for several hours, until all protein synthesis has been arrested, are still able to stimulate the poly U-directed incorporation of phenylalanine into polypeptides at a moderate rate. Activity may be restored to normal levels or above by addition of a soluble enzyme fraction containing transferase II. Our results are in agreement with those of Collier who has recently shown that toxin inactivates transferase II in extracts from rabbit reticulocytes. We have further demonstrated that amino acid incorporation in extracts from intoxicated HeLa cells is limited by their transferase II content whereas, in extracts from normal cells, it is the ribosomes and to a lesser extent sRNA that are limiting. We have found that only soluble transferase II is inactivated by toxin; the ribosome-bound enzyme is resistant.

Studies on the mode of action of diphtheria toxin. V. Inhibition of peptide bond formation by toxin and NAD in cell-free systems and its reversal by nicotinamide.

Inhibition of soluble transferase II activity in cell-free systems by diphtheria toxin and NAD can be prevented or reversed in the presence of a sufficient concentration of nicotinamide. Quantitative studies on inhibition of peptide bond formation in cell-free extracts by toxin and NAD have indicated that two successive reversible reactions are involved. First, toxin and NAD interact mole for mole to form a relatively dissociable complex. This toxin-NAD complex then reacts with transferase II to form an enzymatically inactive product that is but slightly dissociated. In the presence of sufficient nicotinamide, however, the latter complex can be broken down to yield active transferase II once more. Based on the above model, an equation has been derived that accurately predicts the per cent inhibition of amino acid incorporation in cell-free systems at any given toxin and NAD level. The observed inhibition appears to be independent of the sensitivity to toxin of the cell species from which the extracts were derived, and depends only on the toxin and NAD concentrations. Although the model satisfactorily explains inhibition of peptide bond formation by toxin in cell-free systems, further assumptions are needed to explain how still lower concentrations of toxin are able to arrest protein synthesis completely in the living cell.